As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.
Chronic Disease ; Colitis, Ulcerative/therapy* ; Crohn Disease/epidemiology* ; Diarrhea ; Homeodomain Proteins ; Humans ; Inflammatory Bowel Diseases ; Mesenchymal Stem Cells/cytology* ; MicroRNAs ; RNA, Long Noncoding ; Recurrence ; Umbilical Cord/cytology*

Objective:To investigate the effects of recombinant adenovirus with human vascular endothelial growth factor 165 (Ad-hVEGF 165) and recombinant adenovirus with human tissue inhibitor of metalloproteinase 1 (Ad-hTIMP-1) on rats with myocardial infarction (MI) and its mechanism. Methods:A total of 30 healthy 8-week-old male Wistar rats were randomly divided into 5 groups: sham-operated group (sham), virus control group (Ad-Track), Ad-hVEGF 165 group, Ad-hTIMP-1 group and Ad-hVEGF 165+Ad-hTIMP-1 group (hVEGF 165+hTIMP-1) ( n=6 per group). Except the sham group, all rats were ligated the left anterior descending coronary artery to induce MI model with ST-segment elevation and Q waves or T-wave inversion on electrocardiogram and local myocardial whitening. The corresponding recombinant adenovirus comprising 100 μL (1×10 10 VP/100 μL) combined with NaCl solution was injected into the myocardial infarction area at four points respectively. The sham group received no treatment. After 4 weeks, all rats were sacrificed after echocardiography was completed and heart tissues were collected. The expression of hVEGF 165 and hTIMP-1 were detected by immunohistochemistry. The mRNA expression of apoptosis-related factors were detected by real-time PCR. The protein expression of apoptosis-related factors were detected by immunohistochemistry. Differences between groups were determined by One-way analysis of variance. Multiple comparisons between groups were performed using the least significant difference t-test. Results:(1) Both heart rate (HR) (480.83±24.09) beats/min, left ventricular end-diastolic dimension (LVEDD) (6.88±0.44) mm and left ventricular end-systolic dimension (LVESD) (4.85±0.42) mm were increased in the Ad-Track group than those in the sham group (433.16±17.86) beats/min, (6.20±0.45) mm, (4.06±0.70) mm (all P<0.05), and left ventricular ejection fraction (LVEF) (62.70±3.17) % and left ventricular fractional shortening (LVFS) (29.52±1.88) % were significantly decreased in the Ad-Track group than those in the sham group (72.78±5.44)%, (29.52±1.88) % (both P<0.01). Compared with the Ad-Track group, LVEF (71.50±6.23) % and LVFS (36.17±5.27) % in the hVEGF 165-hTIMP-1 group were significantly increased (both P<0.01), and LVEDD (6.22±0.39) mm and LVESD (4.13±0.23) mm were decreased (both P<0.05). LVEF and LVFS in the hVEGF 165-hTIMP-1 group were increased significantly than those in the Ad-hVEGF 165 group (64.65±4.00) %, (30.95±2.57) % (both P<0.05). The mRNA expression of BCL2-associated X protein (Bax), cysteine aspartate specific proteinase 3 (Caspase-3) and BCL-xL/BCL-2-associated death promoter (Bad) in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-Track group ( P<0.01 or P<0.05), and B-cell lymphoma/leukemia-2 (Bcl-2) in the hVEGF 165-hTIMP-1 group were increased than those in the Ad-Track group ( P<0.01). The mRNA expression levels of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were decreased than those in the Ad-hVEGF 165 group (both P<0.05). There was no statistically difference in the mRNA expression of Bax, Caspase-3, Bad, and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). The protein expression of Bax and Caspase-3 in the hVEGF 165-hTIMP-1 group were significantly decreased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.01), and the protein expression of Bcl-2 in the hVEGF 165-hTIMP-1 group was increased than those in the Ad-hVEGF 165 group, the Ad-hTIMP-1 group and the Ad-Track group (all P<0.05). There were no statistically differences in the protein expression of Bax, Caspase-3 and Bcl-2 between the hVEGF 165-hTIMP-1 group and the sham group (all P>0.05). Conclusions:Ad-hVEGF 165 and Ad-hTIMP-1 can improve cardiac contractile function of MI rats and the beneficial effects are largely attributable to inhibiting myocyte apoptosis. The combination of hVEGF 165 and hTIMP-1 may have a synergistic effect on MI.

Femoral neck fractures in pediatric fractures account for less than 1% which is very rare, and its mechanism is commonly caused by high-energy trauma. If children with femoral neck fracture cannot receive timely and effective treatment, they are at high risk of avascular necrosis of the femoral head (AVN), coxa vara, bone nonunion, premature physeal closure, leg length discrepancy and other complications. Surgical treatment is currently preferred over conservative treatment, which has a higher complication rate. Among them, AVN is one of the most common and the most difficult complications to manage. So far, no effective treatment measures and reliable predictors have been reported, and the related factors affecting the occurrence of AVN have also been controversial. Once femoral head necrosis occurs in children, the prognosis is not ideal due to the lack of appropriate treatment methods. Therefore, this paper reviews the research progress on the related factors of AVN after femoral neck fracture in children based on the literature reports in the past decade.

Objective: To observe the effects of recombinant adenovirus with human tissue inhibitor of metalloproteinase-1(Ad-hTIMP-1) on the inflammatory response in rats with myocardial infarction (MI) and explore the related mechanisms. Methods: The male Wistar rats were randomly divided into sham-operated group, saline group, Ad-Track group and Ad-hTIMP-1 group according to the random number table (n=8 each group). MI was induced by ligation of the left anterior descending coronary artery and MI rats were injected with saline, Ad-Track and Ad-hTIMP-1, respectively. Sham-operated rats received similar surgical procedure without ligation of the left anterior descending coronary artery. After 4 weeks, the cardiac function was measured by echocardiography, then rats were sacrificed and hearts were removed for morphological and biological analysis. The morphology of myocardial tissue in each group was detected by HE staining and Masson staining. The mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and C-reactive protein(CRP) were detected by real-time PCR. Immune histochemical staining was performed to observe the protein expression levels of IL-6 and CRP. Results: (1) Left ventricular end systolic dimension derived from echocardiography was increased in saline group ((5.10±0.72) mm) and Ad-Track group ((4.88±0.64) mm) compared to sham-operated group ((4.25±0.46) mm), which was reduced in Ad-hTIMP-1 group ((4.13±0.35) mm, all P<0.05). The left ventricular ejection fraction was (72.46±5.74)%, (64.27±8.52)%, (64.65±3.90)%, and (71.55±6.95)%, the fractional shortening was (36.90±4.97)%, (29.03±3.40)%, (30.95±2.51)%, and (36.31±5.68)% in sham-operated group, saline group, Ad-Track group and Ad-hTIMP-1 group, respectively. The left ventricular ejection fraction and fractional shortening in saline group and Ad-Track group were lower than those in sham-operated group and Ad-hTIMP-1 group (all P<0.05). (2) Necrosis of myocardial cells was not found and a small amount of immune cell infiltration and interstitial fibrosis were observed on HE and Masson stained myocardial sections of Ad-hTIMP-1 group. (3) Real-time PCR showed that mRNA expressions of TNF-α, IL-6, IL-10 and CRP were lower in Ad-hTIMP-1 group than in saline group. mRNA expressions of TNF-α, IL-10 and CRP were lower in Ad-hTIMP-1 group than in Ad-Track group (all P<0.05). (4) Immune histochemical staining showed that protein expressions of IL-6 and CRP were higher in saline group and Ad-Track group than those in Ad-hTIMP-1 group (all P<0.05). Conclusion Recombinant adenovirus Ad-hTIMP-1 can improve cardiac function in rats with myocardial infarction via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-6 and CRP.

OBJECTIVETo explore the effect of VNTR-ZNF and -14C/T variants of the promoter region of the ABCA1 gene on the transcription activity of genes in vitro.

METHODSThe recombinants were constructed by ligating DNA fragment containing VNTR-ZNF ACCCC inserted/deleted allele with or without -14C/T substitution fragments with a PGL2-basic vector containing luciferase reporter gene. The recombinants were then transfected into HepG2 cells using the cationic lipid method. After 48 h, transfected cells were collected and used to detect the luciferase activity.

RESULTSLuciferase activity of PGL2-ZNF-ACCCCDel was greater than that of PGL2-ZNF-ACCCCIns. Luciferase activity of PGL2-ZNFDel-14C was greater than that of PGL2-ZNFDel-14T, PGL2-ZNFIns-14C, PGL2-ZNFIns-14T.

CONCLUSIONCompared with the insertion type, the ACCCC-deleted type of VNTR-ZNF can significantly enhance the transcription activity of ABCA1. And co-transfection of -14 C allele can further enhance this activity.

ATP Binding Cassette Transporter 1 ; genetics ; Base Sequence ; Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Luciferases ; genetics ; metabolism ; Minisatellite Repeats ; genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; genetics ; Zinc Fingers ; genetics

Objective To evaluate the clinical efficacy and adverse reactions of alizarin combined with anti-tuberculosis therapy for multidrug resistant pulmonary tuberculosis (MDR-PTB).Methods A total of 200 confirmed MDR-PTB patients admitted in the Affiliated Hospital of Hangzhou Normal University during June 2013 and June 2015 were enrolled in the study.Patients were randomly divided into study group and control group (100 in each).Both groups were given standard anti -tuberculosis treatment for 8 months, and additional alizarin was given to study group .Chi-square test was used to assess the differences in clinical efficacy, sputum negative conversion rate, cavity closure and lesion absorption rate , as well as the incidence of adverse reactions between two groups ( including patients categorized according to TCM syndrome ). Results There were 39 markedly effective cases, 51 improved cases, 10 ineffective cases in study group, and 22 markedly effective cases, 35 improved cases, 43 ineffective cases in the control group.The total effective rate in study group was significantly higher than that in control group (90% vs.57%, χ2 =28.262, P <0.01).For patients with TCM syndrome differentiation as phlegm -heat stagnating lung and those with qi-stagnation induced blood-stasis, alizarin combination therapy had significantly higher total effective rate than standard anti -tuberculosis treatment (78.78% vs.63.33%, χ2 =7.187, P <0.05;95.74% vs.42.31%, χ2 =73.997, P <0.01), but the difference was not observed in patients with TCM syndrome differentiation as deficiency of qi and blood (95.00% vs.88.89%, χ2 =5.025, P >0.05). There was no significant difference in sputum negative conversion rate between two groups (76% vs.55%,χ2 =2.190, P >0.05).The cavity closure and lesion absorption rate in study group ( 91%) was significantly higher than that in the control group (54%,χ2 =38.294, P <0.01).The adverse reaction rate in study group was 27%, which was significantly lower than that in control group (66%, χ2 =30.570, P <0.01).Conclusion Alizarin in combination with standard anti -tuberculosis therapy can improve the clinical efficacy and reduce adverse reactions in treatment of MDR -PTB.

Objective To observe the effect of Shenfu injection on fluid intake volume of resuscitation therapy for patients with septic shock. Methods The clinic data of 36 patients with septic shock admitted to Department of Critical Care Medicine of the Affiliated Hospital of Hangzhou Normal University from June 2010 to June 2013 were retrospectively analyzed. All the patients were treated with western conventional medicine. Twenty cases treated with western medicine combined with Shenfu injection (intravenous drip 100 mL once daily, half of a month was a therapeutic course) were defined as Shenfu group; the rest 16 cases treated with western medicine only were assigned as control group. The following data after treatment for 6, 24, and 72 hours in the two groups were compared:liquid intake and urine volumes, system vascular resistance index (SVRI), mean arterial pressure (MAP), cardiac index (CI), and case fatality rate in 28 days. Results There were no significant differences in the liquid intake volume in 6 hours after treatment (mL:3 101±219 vs. 3 329±295, P>0.05), the urine volumes in 6, 24 and 72 hours after treatment (mL, 6 hours:701±229 vs. 651±292, 24 hours:1 870±566 vs. 1 697±618, 72 hours:7 396±2 546 vs. 5 987±2 497), and the levels of SVRI in 24 hours after treatment between Shenfu group and control group (kPa·s·L-1·m-2:802±158 vs. 741±106, all P>0.05). The total liquid intake volumes (mL) in 24 hours and 72 hours after treatment in Shenfu group were significantly less than those in the control group (24 hours:4 544±425 vs. 4 996±396, 72 hours:10 985±891 vs. 11 612±807, both P<0.05). The SVRI, MAP, and CI in 72 hours of Shenfu group were significantly higher than those of control group [SVRI (kPa·s·L-1·m-2): 1 361±182 vs. 1 163±183, MAP (mmHg, 1 mmHg = 0.133 kPa): 76.2±6.1 vs. 71.8±6.3, CI (mL·s-1·m-2):76.2±7.5 vs. 70.8±7.2, all P<0.05], and the 28-day mortality rate in Shenfu group was significantly lower than that of control group [25.0%(5/20) vs. 62.5%(10/16), P<0.05]. Conclusion The application of Shenfu injection was favorable to the reduction of liquid intake volume in 72 hours after treatment that may be beneficial to the fluid limitation management in the course of treatment for septic shock.

Chronic exposure to risk factors at the beginning stage of atherosclerosis development can damage endotheli?um and ultimately initiat endothelial dysfunction. Endothelial dysfunction is one of the major mechanisms in atherosclerosis development. High-density lipoprotein (HDL) is a lipoprotein with complicated function and is composed of a variety of pro?teins and lipids. Epidemiological studies showed an inverse correlation between HDL and atherosclerosis. The protective role of HDL on endothelium might related to its function in reversing cholesterol transport, reducing peripheral cholesterol accu?mulation, preventing foam cells formation, dilating vessels, antioxidant and anti-inflammation, all of which antagonize devel?opment of atherosclerosis. But HDL obtained from patients with cardiovascular disease which has known dysfunctional HDL may induce endothelial dysfunction. This review addresses the relationships between functional HDL or dysfunctional HDL with the endothelial function.

Objective To study the role of N‐acetylcysteine (NAC) in protecting rats against con‐trast‐induced acute kidney injury .Methods Forty‐five adult Wistar rats were randomly divided into control group ,model group and NAC group (15 in each group) .Their serum levels of creati‐nine ,CRP ,TNF‐a were measured before ,and 48 and 72 h after contrast medium injection .The an‐imals were killed 72 h after contrast medum injection .Their serum levels of malondialdehyde , SOD ,NO were measured .Eexpressions of Bax and Bcl‐2 were detected .Results The serum levels of creatinine ,CRP ,TNF‐a ,malondialdehyde and the expression level of Bax were significantly higher in model group and NAC group than in control group ,and in model group than in NAC group after contrast injection (P< 0 .05) .The serum levels of SOD and NO and the expression level of Bcl‐2 were significantly lower in model group and NAC group than in control group ,and in model group than in NAC group after constrast injection (P< 0 .05) .Immunohistochemistry demonstrated that the TGFβ1 expression level was significantly higher in model group and NAC group than in control group and was significantly lower in NAC group than in model group .Con‐clusion NAC can protect rats against kidney injury and reduce contrast‐induced acute kidney in‐jury by inhibiting inflammation ,oxidation ,apoptosis and cytokines .

Objective To investigate the therapeutic effect of Ad-hVEGF165 on the endothelial cells dysfunction induced by homocysteine (Hcy) and related molecular mechanisms.Methods Human umbilical vein endothelial cells CRL-1730 were treated with Hcy at different concentrations (0,0.05,1.00 mmol/L) for 24 h.The same concentration of Hey,Ad-Track and Ad-hVEGF165 were added to the cells in the following groups:blank group,Hcy0.05 group,Hcy1.00 group,Ad-Track group,Hey0.05 + Ad-Track group,Hcy1.00 + Ad-Track group,Ad-hVEGF165 group,Hey0.05 + Ad-hVEGF165 group,Hcy1.00 + AdhVEGF165 group for 48 h.The mRNA and protein expressions of eNOS and DDAH2 were detected by realtime PCR and Western blot.The correlations of mRNA and protein expressions between endothelial nitric oxide synthase (eNOS) and dimethylarginine dimthylaminohydrolase (DDAH)2 were evaluated by Pearson correlation analysis.Results Compared with blank group and Ad-hVEGF465 group,the mRNA and protein expressions of eNOS were decreased in Hcy0.05 group and Hcy0.05 + Ad-hVEGF165 group (both P ＜ 0.05),and the mRNA and protein expressions of DDAH2 in cells treated with 0.05 mmol/L and 1.00 mmol/L Hcy were reduced as well(all P ＜ 0.05).DDAH2 mRNA and protein expression are increased (all P ＜ 0.05) in Ad-hVEGF165 group compared with the blank group and Ad-Track,Hcy0.05 + Ad-hVEGF165 and Hcy0.05 group compared with Hcy0.05 + Ad-Track group,Hcy1.00 + Ad-hVEGF165 and Hcy1.00 group compared with Hcy1.00 + Ad-Track group.The mRNA and protein expressions of eNOS and DDAH2 were uncorrelated under the effect of Hcy(r =0.057 and 0.449,both P ＞0.05) and VEGF (r =0.284 and 0.432,both P ＞ 0.05).Conclusion Recombinant adenovirus Ad-hVEGF165 could reverse Hcy-induced endothelial cells dysfunction via upregulating the expressions of eNOS and DDAH2.